PLOS Genetics: Statistical Estimation of Correlated Genome Associations to a Quantitative Trait Network
Correlated Genome Associations to Quantitative Trait #Network (QTN) http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1000587
Uses fused #lasso for estimation of relationships
Kim & Xing (’09) provide a new method for calculating how genetic
markers associate with phenotypes by incorporating phenotype
connectivity features into the correlation structure between markers
and phenotypes. Their model attempts to quantify pleiotropic
relationships between different phenotypes and assumes a common
genotypic origin for the existence of clusters of correlated
phenotypes, which their algorithm uses to reduce the number of
significant genetic markers. In particular, Kim and Xing present a
method for performing quantitative trait analysis that implements two
novel approaches to inferring the contribution of a
[marker/allele/SNP/gene/locus] to a quantitative trait. The first is
organization of traits into a quantitative trait network (QTN). The
second is the utilization of fused lasso, a variation of multivariate
regression that seeks to minimize the number of non-zero coefficients
and least squared error. These two approaches are combined in an
attempt to minimize noise (in the form of small coefficients for SNP’s
that don’t really make a contribution) and focus on truly relevant
SNP’s while dealing with the correlated nature of quantitative
traits. Based on two datasets – simulated HapMap data and
data from the Severe Asthma Research Program – the authors show marked
improvement in accuracy and reduction of false positives over simpler
multivariate regression methods.